Considerable evidence has accumulated which suggests that neurotensin (NT), an endogenous peptide, exhibits actions similar to neuroleptic drugs. These similarities between NT and neuroleptic agents are of particular interest in view of the reports by several research groups that this peptide is found in its highest concentration in the nucleus accumbens, brain region receiving a major termination of the mesolimbic dopamine system, dysfunction of which is probably contributory to the schizophrenic process. This proposal shall extend the comparison between these agents using biochemical and behavioral techniques. The effects of NT on neuroleptic receptor binding, and the effects of neuroleptics on NT binding will be analyzed. The effects of NT in several behavioral paradigms used as neuroleptic screens will be investigated. These include apomorphine/amphetamine induced behaviors, discrete trial conditioned avoidance responding and brain self-stimulation behavior. In addition, the precise distribution of authentic NT in rat CNS, human and postmortem schizophrenic brain tissue with corresponding age and sex matched controls will be determined. This work shall determine whether NT acts as an endogenous modulator of dopaminergic neurotransmission. This project should provide valuable insight concerning the physiological function of this endogenous neuropeptide.